Congestive heart failure is a clinical syndrome characterized by a constellation of features which among many others includes peripheral edema, elevated resting sympathetic nerve activity and abnormal sympathetic nerve activity during exercise. Reduced exercise tolerance with increased and earlier fatigue and greater metabolite production during exercise are also seen. In a previous set of studies, we have shown that metabolite sensitive afferents (metaboreceptors) which stimulate sympathetic nerve activity are desensitized in congestive heart failure. Despite this desensitization, the rise in sympathetic nerve activity muscle sympathetic nerve activity is normal during exercise in congestive heart failure, meaning that a mechanism other than metaboreceptors is leading to the muscle sympathetic nerve activity augmentation. We plan to pursue a series of experiments to further elucidate the role of interstitial volume and pressure in congestive heart failure. These experiments will involve alternately congesting the arm by venous occlusion (high pressure, high volume) and decongesting, utilizing a commercially available device for treating edema (low pressure, low volume). We will also use a sealed plexiglass tank around the forearm which can either provide elevated pressure high pressure, low volume) or negative pressure (low pressure, high volume). Studies will be done in both normal individuals and subjects with congestive heart failure. These designs will allow us to better understand the role of mechanoreceptors in exercise in both populations and to elucidate how interstitial volume and pressure interact with the sympathetic nervous system in congestive heart failure.